POS1041 LONG-TERM EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS REFRACTORY TO BIOLOGIC THERAPIES: 2-YEAR RESULTS FROM THE PHASE 3 SELECT-PsA 2 STUDY
Authors: P. J. Mease, A. Setty, K. Papp, F. Van den Bosch, S. Tsuji, M. Keiserman, X. Bu, L. Chen, R. Mccaskill, E. Mcdearmon-Blondell, P. Wung, W. Tillett
Journal: Annals of the Rheumatic Diseases (2022)

Background Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to ≥1 biologic disease-modifying antirheumatic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study. 1 Objectives To evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECT-PsA 2. Methods Pts were randomized to UPA 15 mg (UPA15), UPA 30 mg (UPA30), or placebo (PBO) for 24 wks; PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatment-emergent adverse events (TEAEs) were summarized for pts who received ≥1 dose of study drug using visit-based cut-off at wk 104. Results A total of 641 pts received ≥1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks 1 (Table 1). Similarly, mean change from baseline in HAQ-DI, patient’s assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 (Figure 1) were consistent with that reported at wk 56. 1 Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information; however, the patient had recently been diagnosed with ovarian cancer) and 2 with UPA30 (pancytopenia and COVID-19 pneumonia). Table 1. Efficacy Endpoints at Week 104 Endpoint UPA15 (n=211 ) UPA30 (n=218 ) Proportion of Pts (%) a NRI AO NRI AO ACR20 55.5 80.3 54.6 81.8 ACR50 44.5 62.9 39.9 59.4 ACR70 23.2 32.2 21.6 31.5 Minimal Disease Activity (MDA) 29.4 41.3 33.9 49.3 PASI75 b 47.7 69.8 52.7 81.1 PASI90 b 37.7 55.2 44.3 67.8 PASI100 b 23.1 35.4 35.9 55.6 Resolution of enthesitis by LEI c 39.8 67.8 37.5 68.4 Resolution of dactylitis by LDI d 54.5 97.4 52.0 96.9 Change from BL e MMRM AO MMRM AO Health Assessment Questionnaire - Disability Index (HAQ-DI) -0.36 -0.39 -0.50 -0.53 Patient’s assessment of pain (numeric rating scale) -2.7 -3.0 -2.9 -3.1 Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) f -2.6 -3.0 -2.6 -2.9 Ankylosing Spondylitis Disease Activity Score (ASDAS) f -1.4 -1.7 -1.3 -1.5 ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology criteria; AO, as observed; BL, baseline; LDI, Leeds Dactylitis Index; LEI, Leeds Enthesitis Index; MMRM, mixed effect model repeated measurement; NRI, non-responder imputation; PASI75/90/100, ≥75%/90%/100% improvement in Psoriasis Area and Severity Index; pts, patients; UPA, upadacitinib. a Data shown as NRI and AO for binary endpoints. b For pts with psoriasis affecting ≥3% of body surface area at BL. c For pts with LEI &gt;0 at BL; resolution LEI=0. d For pts with LDI &gt;0 at BL; resolution LDI=0. e Data shown as MMRM (LS mean) and AO (mean) for continuous endpoints. f For pts with psoriatic spondylitis at BL. Conclusion In PsA pts with prior inadequate response or intolerance to ≥1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to 2 years of treatment. No new safety signals were identified in this long-term extension. References [1]Mease PJ, et al. Rheumatol Ther . 2021;8:903-19. Acknowledgements AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial ( NCT03104374 ). AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Monica R.P. Elmore, PhD of AbbVie. Disclosure of Interests Philip J Mease Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Arathi Setty Shareholder of: Employee of AbbVie and may hold stock options, Employee of: Employee of AbbVie, Kim Papp Speakers bureau: AbbVie, Akros, Allergan, Almirall, Amgen, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, Genentech/Roche, Janssen, Kyowa Kirin, LEO, Meiji, MSD, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, Takeda, UCB, and Valeant, Consultant of: AbbVie, Akros, Allergan, Almirall, Amgen, Arcutis, Avillion, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, Genentech/Roche, GSK, Janssen, Kyowa Kirin, LEO, Meiji, MSD, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, Takeda, UCB, and Valeant, Grant/research support from: AbbVie, Akros, Allergan, Almirall, Amgen, Arcutis, Avillion, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, Genentech/Roche, GSK, Janssen, Kyowa Kirin, LEO, Meiji, MSD, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, Takeda, UCB, and Valeant, Filip van den Bosch Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, and UCB, Shigeyoshi Tsuji Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, and UCB, Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, and UCB, Grant/research support from: AbbVie, Eli Lilly, Janssen, Novartis, and UCB, MAURO KEISERMAN Speakers bureau: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Xianwei Bu Shareholder of: Employee of AbbVie and may hold stock options, Employee of: Employee of AbbVie, Liang Chen Shareholder of: Employee of AbbVie and may hold stock options, Employee of: Employee of AbbVie, Reva McCaskill Shareholder of: Employee of AbbVie and may hold stock options, Employee of: Employee of AbbVie, Erin McDearmon-Blondell Shareholder of: Employee of AbbVie and may hold stock options, Employee of: Employee of AbbVie, Peter Wung Shareholder of: Employee of AbbVie and may hold stock options, Employee of: Employee of AbbVie, William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Celgene, Eli Lilly, and Janssen